Hydrochloric Acid → Tert-butyl N-[(3S)-2-oxoazetidin-3-yl]carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of Boc-L-serine (10.3 g, 50 mmol) in 75 mL of H2O:t-BuOH (2:1) is added methoxyamine hydrochloride (23 g, 75 mmol) and 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (9.6 g, 50 mmol). After 2 hours, the solution is saturated with NaCl. The solution is extracted with EtOAc. The organic layer is dried over MgSO4, filtered and concentrated. The resulting crude material is dissolved in 50 mL of pyridine and cooled to 0° C. To the solution is added methane sulfonyl chloride (7.44 g, 65 mmol). After 1 hour, the solution is poured into 100 mL of cold 1 N HCl (aq.). The solution is diluted with EtOAc. The layers are separated and the organic layer is washed with 1 N HCl, saturated NaHCO3 and saturated NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The resulting crude material is dissolved in 50 mL of acetone and added dropwise to a solution of K2CO3 (20.7 g, 150 mmol) in 900 mL of acetone at reflux. After 1 hour, the solution is cooled to ambient temperatures. The solution is filtered through Celite. The collected organic solution is washed with 1 N HCl, saturated NaHCO3 and saturated NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The resulting solid is dissolved in 20 mL of THF and added dropwise to an ammonia solution containing sodium (2.6 g, 113 mmol) at -78° C. After the blue color has dissipated, the solution is stirred for an additional 10 minutes. To the reaction mixture is added NH4Cl (13.4 g, 250 mmol) and the solution is allowed to warm to ambient temperatures. The solution is filtered. The collected solution is concentrated. The resulting residue is recrystallized from EtOAc to give the title compound (2 g, 11 mmol) as a white solid.

Provenance & Evidence